Specific pulmonary lesions may be produced in experimental animals by exposure to the gases oxygen or ozone or by parenteral administration of a chemical, paraquat. The lesions which result from these 3 model compounds all follow a similar histopathological pattern of development and are throught to result from oxidant-mediated damage to pulmonary membranes and/or pulmonary surfactant. To be specifically examined are the microsomal enzyme complexes responsible for pulmonary xenobiotic metabolism and lipid metabolism (i.e. the mixed function oxidases). This should establish whether observed alterations are specific for microsomal lipid metabolism (desaturation) or are a generalized effect on pulmonary mixed function oxidation. Also the enzymes responsible for the activation of oxygen to superoxide and peroxide and the respective catabolic enzymes, superoxide dismutase and catalase, will be examined for possible common involvement in the production of the characteristic lesions in each of the 3 model systems. Finally, the isolated perfused lung preparation will be utilized to evaluate; 1) changes in whole lung mixed-function oxidation during development of the lesions, 2) alterations in distribution of chemicals and drugs into the diseased lungs. Approaches to protection against the development of these lesions will also be investigated by altering in vivo levels of the various enzyme systems and then evaluating the quantity of protection with the in vitro enzyme systems and the isolated, perfused lung preparation.